Sex Specific Differences in GABA and Glutamate Levels in Response to Cigarette Smoke

Introduction Men and women behave differently in response to cigarette smoke. Women are quicker to develop nicotine tolerance than men [1] and have higher rate of relapse [2,3]. Nicotine, a major substance of smoke binds to nicotinic acetylcholine receptors (nAChRs); ligandgated cation channels [4] and modulates its activity. Nicotine also up-regulates nAChRs, which is more readily reflected in males than females [5]. Chronic smoking also alters circulating sex-hormones [6], which in turn mediates nAChRs activity. Progesterone has been shown to inhibit nAChRs activity [7] and estrogen but not testosterone can block antinociceptive effect of nicotine in female mice [8,9]. Although, dopaminergic system is involved in nicotine addiction, involvement of glutamatergic and GABAergic system is crucial for long term addiction [10]. GABA and glutamate are major inhibitory and excitatory neurotransmitters and are involved in many neurological pathways [11,12]. Nicotine modulates release of GABA and glutamate through nAChRs [13]. This study aims to measure gamma amino butyric acid (GABA) and glutamate in men and women chronic smokers of African American (AA) descent. GABA is known to control dopamine release through receptors present on dopamine releasing neurons while Glutamate, a neurotransmitter associated with memory in the brain, causes increase in alertness and pleasure through acetyl choline and dopamine, respectively [14].